Dynamic covalent self-assembly of mechanically interlocked molecules solely made from peptides

Mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, have captured the attention of chemists both from a synthetic perspective and because of their role as simple prototypes of molecular machines. Although examples exist in nature, most synthetic MIMs are made from artificial building blocks and assembled in organic solvents. Synthesis of MIMs from natural biomolecules remains highly challenging. Here we report on a synthesis strategy for interlocked molecules solely made from peptides—mechanically interlocked peptides (MIPs). Fully peptidic, cysteine-decorated building blocks were self-assembled in water to generate disulfide-bonded dynamic combinatorial libraries consisting of multiple different rotaxanes, catenanes and daisy chains as well as more exotic structures. Detailed NMR spectroscopy and mass spectrometry characterization of a [2]catenane comprised of two peptide macrocycles revealed that this structure has rich conformational dynamics reminiscent of protein folding. Thus, MIPs can serve as a bridge between fully synthetic MIMs and those found in nature.